Caudal (Cdx) transcription factors have been implicated in the development of trunk and tail structures across all major animal groups by controlling the generation, sequential addition and identity of posterior body segments. We have shown that knock down of Cdx function in a vertebrate embryo additionally causes a non- segmented region of the nervous system, namely the spinal cord, to become segmented and to form ectopic hindbrain rhombomeres in the trunk. In reciprocal gain-of-function experiments we have shown that Cdx- overexpression is sufficient to cause a segmented structure, namely the hindbrain, to lose aspects of its segmental character and take on features of the spinal cord. We propose that the function of Cdx factors in the vertebrate nervous system may be to prevent the development of segments analogous to hindbrain rhombomeres, thus allowing the formation of an unsegmented spinal cord. We additionally propose that Cdx factors normally function to limit the size of the hindbrain and spinal cord territories, allowing for the proper patterning of the Central Nervous System. In this proposal we will place the Cdx genes within a working context of what is already known about hindbrain development in which an extensive literature already exists. In addition we hope to determine the important cellular and genetic interactions involving Cdx function within the spinal cord and to show that these interactions may be conserved within vertebrates to allow for the specification of the posterior neural tube. In this proposal, we use a variety of molecular, genetic and embryological techniques to address this previously unsuspected role of Cdx factors within the nervous system. Public Health Relevance: Structural birth defects have been shown to increase the rates of such disorders as autism and mental retardation in surviving patients. Neural tube defects often develop within the first few weeks of pregnancy. Anencephaly, spina bifida and other neural tube defects are known to have both genetic and environmentally- induced components of susceptibility.